Pre-clinical evaluation of a whole-parasite vaccine to control human babesiosis.

Babesia spp. are tick-transmitted intra-erythrocytic protozoan parasites that infect humans and animals, causing a flu-like illness and hemolytic anemia. There is currently no human vaccine available.

Poly(amino acids) as a potent self-adjuvanting delivery system for peptide-based nanovaccines.

To be optimally effective, peptide-based vaccines need to be administered with adjuvants. Many currently available adjuvants are toxic, not biodegradable; they invariably invoke adverse reactions, including allergic responses and excessive inflammation. A nontoxic, biodegradable, biocompatible, self-adjuvanting vaccine delivery system is urgently needed.

Mannosylated liposomes formulated with whole parasite P. falciparum blood-stage antigens are highly immunogenic in mice.

The development of a blood-stage malaria vaccine has largely focused on the subunit approach. However, the limited success of this strategy, mainly due to antigenic polymorphism and the failure to maintain potent parasite-specific immune responses, indicates that other approaches must be considered. Whole parasite (WP) vaccines offer many advantages over sub-units; they represent every antigen on the organism, thus limiting the effects of antigenic polymorphism, and similarly they compensate for individual Immune-Response (Ir) gene-regulated non-responsiveness to any particular antigen.

Induction of Plasmodium-Specific Immune Responses Using Liposome-Based Vaccines.

In the development of vaccines, the ability to initiate both innate and subsequent adaptive immune responses need to be considered. Live attenuated vaccines achieve this naturally, while inactivated and sub-unit vaccines generally require additional help provided through delivery systems and/or adjuvants. Liposomes present an attractive adjuvant/delivery system for antigens.

Development of New Gonadotropin-Releasing Hormone-Modified Dendrimer Platforms with Direct Antiproliferative and Gonadotropin Releasing Activity.

Gonadotropin-releasing hormone (GnRH) agonists (e.g., triptorelin) are used for androgen suppression therapy.

Lipid core peptide/poly(lactic-co-glycolic acid) as a highly potent intranasal vaccine delivery system against Group A streptococcus.

Rheumatic heart disease represents a leading cause of mortality caused by Group A Streptococcus (GAS) infections transmitted through the respiratory route. Although GAS infections can be treated with antibiotics these are often inadequate. An efficacious GAS vaccine holds more promise, with intranasal vaccination especially attractive, as it mimics the natural route of infections and should be able to induce mucosal IgA and systemic IgG immunity.

A semi-synthetic whole parasite vaccine designed to protect against blood stage malaria.

Unlabelled: Although attenuated malaria parasitized red blood cells (pRBCs) are promising vaccine candidates, their application in humans may be restricted for ethical and regulatory reasons. Therefore, we developed an organic microparticle-based delivery platform as a whole parasite malaria-antigen carrier to mimic pRBCs. Killed blood stage parasites were encapsulated within liposomes that are targeted to antigen presenting cells (APCs).

Highly Immunogenic Trimethyl Chitosan-based Delivery System for Intranasal Lipopeptide Vaccines against Group A Streptococcus.

Background: Group A streptococcus (GAS) primarily colonizes the mucosal region of the upper respiratory tract, slowly leading to systemic infections. Thus, GAS-specific antibody responses are desirable at mucosal sites for early prevention against GAS colonization.

Methods: Herein, we developed a potent nanoliposomes-based delivery system for mucosally active lipid core peptide (LCP)-based vaccines.

Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus.

Unlabelled: Group A streptococcus (GAS), an exclusively human pathogen, causes a wide range of diseases ranging from trivial to life threatening. Treatment of infection is often ineffective following entry of bacteria into the bloodstream. To date, there is no vaccine available against GAS.

Synthesis of Mannosylated Lipopeptides with Receptor Targeting Properties.

Present on the surface of antigen presenting cells (APCs), the mannose receptor (MR) has long been recognized as a front-line receptor in pathogen recognition. During the past decade many attempts have been made to target this receptor for applications including vaccine and drug development. In the present study, a library of vaccine constructs comprising fluorescently labeled mannosylated lipid-dendrimers that contained the ovalbumin CD4(+) epitope, OVA(323-339), as the model peptide antigen were synthesized using fluorenylmethyloxycarbonyl (Fmoc) solid phase peptide synthesis (SPPS).

Investigation of structure-activity relationships of synthetic anti-gonadotropin releasing hormone vaccine candidates.

The immunoneutralization of gonadotropin-releasing hormone (GnRH) can be used for the treatment of human hormone-dependent male and female cancers or as immunocontraceptives in animals. Vaccine candidates 1 [Th(K-LP)GnRH], 2 [GnRH(K-LP)Th], 3 [GnRH(K-Th)LP], and 4 [Th(K-GnRH)LP] (for which K=lysine, LP=lipopeptide Ser-Ser-C16 -C16 , and Th=T helper cell epitope influenza HA2), were synthesized by assembling a CD4(+) T helper cell epitope (Th), GnRH, and an adjuvanting lipid moiety (LP) in various spatial arrangements. All compounds were efficiently taken up by antigen-presenting cells with significant immunogenicity without an external adjuvant.

Polyacrylate-based delivery system for self-adjuvanting anticancer peptide vaccine.

Vaccination can provide a safe alternative to chemotherapy by using the body's natural defense mechanisms to create a potent immune response against tumor cells. Peptide-based therapeutic vaccines against human papillomavirus (HPV)-related cancers are usually designed to elicit cytotoxic T cell responses by targeting the HPV-16 E7 oncoprotein. However, peptides alone lack immunogenicity, and an additional adjuvant or external delivery system is required.

Self-adjuvanting vaccine against group A streptococcus: application of fibrillized peptide and immunostimulatory lipid as adjuvant.

Peptides are of great interest to be used as vaccine antigens due to their safety, ease of manufacturing and specificity in generating immune response. There have been massive discoveries of peptide antigens over the past decade. However, peptides alone are poorly immunogenic, which demand co-administration with strong adjuvant to enhance their immunogenicity.

Self-adjuvanting therapeutic peptide-based vaccine induce CD8+ cytotoxic T lymphocyte responses in a murine human papillomavirus tumor model.

Vaccine candidates for the treatment of human papillomavirus (HPV)-associated cancers are aimed to activate T-cells and induce development of cytotoxic anti-tumor specific responses. Peptide epitopes derived from HPV-16 E7 oncogenic protein have been identified as promising antigens for vaccine development. However, peptide-based antigens alone elicit poor cytotoxic T lymphocyte (CTL) responses and need to be formulated with an adjuvant (immunostimulant) to achieve the desired immune responses.

Liposomes as nanovaccine delivery systems.

Since the discovery of liposomes by Alec Bangham in mid-1960s, these phospholipid vesicles have been widely used as pharmaceutical carriers. Liposomes have been extensively studied in the vaccine delivery field as a carrier and an immune stimulating agent. Liposomes are usually formulated as nanoparticles, mimicking the properties of pathogens, and have the ability to induce humoral and cell-mediated immune responses.

Apoptogenic activity of ethyl acetate extract of leaves of Memecylon edule on human gastric carcinoma cells via mitochondrial dependent pathway.

Objective: To evaluate the anti-proliferative and apoptogenic activity of ethyl acetate extract from the leaves of Memecylon edule (EtAc-LME) in MKN-74, NUGC gastric cancer cells and non cancerous gastric mucous cells (GES-1), and to explore the mechanism of EtAc-LME induced apoptosis.

Methods: The mechanism of EtAc-LME induced apoptosis was explored by analysing the activation of pro-caspases, PARP cleavage, expression of cytochrome-c (Cyt-c) was determined by western blotting, mRNA expression of Bcl-2, Bax by RT-PCR, loss of mitochondrial potential using DiOC6 dye, annexin binding assay and its influence on cell cycle arrest by flow cytometry.

Results: The results indicated that EtAc-LME inhibited the gastric cancer cell growth in dose-dependent manner and cytotoxicity was more towards the gastric cancer cells (NUGC and MKN-74) compared to normal gastric cells (GES-1), suggesting more specific cytotoxicity to the malignant cells.

Liposome-based delivery system for vaccine candidates: constructing an effective formulation.

The discovery of liposomes in 1965 by Bangham and coworkers changed the prospects of drug delivery systems. Since then, the application of liposomes as vaccine delivery systems has been studied extensively. Liposomal vaccine delivery systems are made up of nano- or micro-sized vesicles consisting of phospholipid bilayers, in which the bioactive molecule is encapsulated/entrapped, adsorbed or surface coupled.